Cigarette smoking and other forms of tobacco exposure are the leading preventable causes of morbidity and mortality in our society, Epidemiological surveys have shown that over 90% of people who ever smoked and 70% of regular smokers initiated smoking before the age of 18. Research also indicates that early initiation of smoking may lead to more severe form of nicotine dependence and reduced likelihood of quitting smoking in later life. Therefore, smoking during adolescence not only relates to the younger population, but also to the long-term physical and mental health of adults. Given the socioeconomic and psychosocial burden associated with adolescent smoking, early and effective intervention is critical. Despite the evidence that nicotine addiction begins during adolescence, little work has been done on developing interventions. Using a randomized, double-blind, placebo-controlled design, this investigation seeks to evaluate whether bupropion, an antidepressant drug that is also effective for smoking cessation in adults, is helpful in reducing smoking in depressed adolescents. In addition to examining the short-term effect of bupropion on smoking cessation, bupropion's effect on smoking cessation status and clinical course of depression will be evaluated at 6 months. The study also aims to examine the relationship between hypothalamic-pituitary-adrenal (HPA) activity and smoking cessation in response to short-term treatment with bupropion in this population. To our knowledge, this proposal represents the first investigation to examine the role of pharmacotherapy for cigarette smoking in depressed youngsters. By including depressed adolescents, the study will focus on a group known to be at high risk for smoking. Data also suggest that adult depressed patients may be more treatment-resistant to smoking cessation interventions. The study also aims to identify subgroups of depressed adolescents with differential response to bupropion. Such information potentially would be helpful in the development and testing of more specific treatments for the different groups of adolescent smokers. More focused and effective interventions early in the course of the disorder might be helpful in potentially reducing the long-term morbidity and mortality stemming from teenage smoking. Results of the proposed study might lead to treatment for both depression and nicotine dependence in adolescent patients.